Transcription Activation at Bacterial Promoters


Bacterial genomes encode thousands of genes whose expression is regulated in response to changes in the environment. Much of this regulation takes place at the level of the initiation of transcription of specific genes. Bacteria use hundreds of different proteins to activate transcription by a variety of mechanisms.

Keywords: RNA polymerase; promoters; transcription initiation; σ factors; transcription activators; nucleoid‐associated proteins

Figure 1.

RNA polymerase–promoter interactions. (a) Structure of Thermus aquaticus RNA polymerase holoenzyme docked to promoter DNA, from studies by (Seth Darst) and co‐workers. The locations of domains 2, 3 and 4 of the σ subunit (shown as orange ribbons) and their interactions with the −10, extended −10 and −35 elements (highlighted in red) are shown. Note that αCTD and σ domain 1 are not seen in the T. aquaticus RNA polymerase structure. (b) Scheme that illustrates the subunit structure of RNA polymerase holoenzyme and the disposition of the different subunits that make contact with a bacterial promoter. The consensus sequences of the conserved promoter DNA elements are also shown. The σ subunit is comprised of 4 domains, and recognizes the −10, extended −10 and −35 elements. Each α subunit consists of an N‐terminal domain (αNTD) and a C‐terminal domain (αCTD) joined by a linker. The two αCTDs bind to A/T‐rich UP‐elements at many promoters. The β and β′ subunits comprise the active site of the enzyme. The ω subunit is thought to act as a chaperone to help the β′ subunit to fold correctly. The horizontal arrow indicates the direction of transcription and its startpoint.

Figure 2.

Mechanisms of transcription activation. (a) Class I activation. Class I activators bind upstream of their target promoters and recruit RNA polymerase by contacting the C‐terminal domain of one of its α subunits. (b) Class II activation. Class II activators bind close to the −35 element of target promoters and activate transcription by contacting domain 4 of the σ subunit. (c) Activation by pre‐recruitment. Some activators bind directly to RNA polymerase before it binds to promoter DNA. Such activators can alter the DNA‐binding specificity of RNA polymerase, for example by masking the DNA‐binding surface of the α subunit and replacing it with the DNA‐binding domain of the activator. (d) Activation at σ54‐dependent promoters. RNA polymerase containing σ54 can form a closed complex at a target promoter but is unable to form an open complex. Activators that function with this form of RNA polymerase bind to the DNA well upstream of the promoter, and, in order for them to contact RNA polymerase, a loop must form in the intervening DNA. The activators are ATPases, and direct contacts between the activator and σ54 drive a series of ATP‐driven conformational changes that promote open‐complex formation. (e) Activation by restructuring DNA. If the −10 and −35 elements are not properly aligned, RNA polymerase cannot initiate transcription. Transcription is stimulated by activators that bind between the −10 and −35 elements and alter the shape of the intervening DNA so that correct alignment is restored.

Figure 3.

Activation by CRP. (a) Structure of E. coli CRP bound to its target DNA, from studies by (Tom Steitz) and co‐workers. The figure shows a CRP dimer, with the three activating regions, that can contact RNA polymerase, highlighted. In this view, AR1 (shown in blue) is visible on the left‐hand monomer, and AR2 (shown in green) and AR3 (shown in yellow) are visible on the right‐hand monomer. (b) Activation by CRP at a Class I promoter. The CRP‐binding site is located upstream of the RNA polymerase‐binding site. AR1 of the downstream CRP subunit interacts with the C‐terminal domain of one of the RNA polymerase α subunits and so recruits RNA polymerase to the promoter. (c) Activation by CRP at a Class II promoter. The CRP‐binding site is located at position −41.5. AR1 of the upstream CRP subunit contacts the C‐terminal domain of one of the RNA polymerase α subunits, AR2 of the downstream subunit contacts the N‐terminal domain of one of the RNA polymerase α subunits, and AR3 of the downstream subunit contacts domain 4 of the σ subunit.

Figure 4.

Co‐dependence mechanisms. Transcription initiation at many promoters requires two or more activators. The figure illustrates different mechanisms by which two activators (A and B) can cooperate to regulate a single promoter. (a) The binding of each activator to its target site in the DNA is dependent on the binding of the other. Only when both activators are present will a stable activator:DNA complex be formed. (b) The binding of one activator (B) may trigger the repositioning of the other (A), moving it from a location where it is unable to activate transcription, to a location where it is able to activate transcription. (c) The binding of one activator (B) to the promoter may alter the trajectory of promoter DNA such that the second activator (A) is able to make contact with RNA polymerase. (d) Two or more determinants are needed to provide sufficient contacts for RNA polymerase to be recruited, and these are provided by two or more transcription factors. e.g. a Class I activator can act in concert with a Class II activator (i), or with a second Class I activator (ii). (e) The second transcription activator (B) may counteract the action of a repressor (R) that is interfering with the function of the first activator (A).

Figure 5.

Regulation of transcription factors. For transcription activation to act as a ‘genetic switch’, the activity of each transcription activator must be controlled. The figure illustrates different mechanisms used to ensure that activators switch on genes in response to the correct signal. (a) Regulation by binding of a small ligand. Some activators are toggled between an active and inactive form by binding a small signal molecule, such as cyclic adenosine monophosphate (cAMP). Typically, the small molecule causes a conformational change that affects an essential function such as DNA‐binding specificity. In this example, interaction with a small ligand converts the activator from an inactive form that is unable to bind to its target sequence to an active, sequence‐specific DNA‐binding form. (b) Regulation by covalent modification. Some activators are converted between active and inactive forms by covalent modification (e.g. phosphorylation by a kinase that senses a particular signal). Typically, the covalent modification affects an essential function such as DNA‐binding specificity. In this example, the activator is converted from an inactive form, that is unable to bind to its target sequence, to an active, sequence‐specific DNA‐binding form by phosphorylation of its receiver module. (c) Regulation by intracellular protein concentration. The ability of some activators to regulate gene expression is controlled by their concentration. In this example, the activator is produced constitutively and its steady state concentration is kept low because the activator is rapidly degraded by proteases (P). If the proteases are prevented from degrading the activator its concentration in the cell rapidly rises. (d) Regulation by restriction of cellular location. The activity of some regulatory proteins is controlled by proteins that sequester them to locations from which they cannot activate transcription. In this example, σ28 is prevented from binding to RNA polymerase by a complex of proteins that hold it at the cell membrane. In response to an appropriate signal, the complex releases σ28, allowing it to activate transcription. (e) Regulation by anti‐σ factors. Anti‐σ factors regulate σ factor activity by forming a complex that prevents the σ factor binding to RNA polymerase. In response to an appropriate signal, the anti‐σ factor releases the σ factor, allowing it to activate transcription of its target genes. The mechanism by which the σ:anti‐σ complex is disrupted often involves a third protein, termed an anti‐anti‐σ, which binds to the anti‐σ factor more tightly than the σ factor. This mechanism is often referred to as ‘partner switching’.


Further Reading

Baumberg S (1998) Procaryotic Gene Expression. In Frontiers of Molecular Biology series, vol. 21. Oxford: Oxford University Press.

Browning D and Busby S (2004) The regulation of bacterial transcription initiation. Nature Reviews Microbiology 2: 57–65.

Gross C, Chan C, Dombroski A et al. (1998) The functional and regulatory roles of sigma factors in transcription. Cold Spring Harbor Symposium on Quantitative Biology 43: 141–155.

Hughes K and Mathee K (1998) The anti‐sigma factors. Annual Review of Microbiology 52: 231–286.

Lawson C, Swigon D, Murakami K et al. (2004) Catabolite activator protein: DNA binding and transcription activation. Current Opinion in Structural Biology 14: 10–20.

Lloyd G, Landini P and Busby S (2001) Activation and repression of transcription initiation in bacteria. Essays in Biochemistry, vol. 37, chap. 2, pp. 17–32. London: Portland Press.

Murakami K and Darst S (2003) Bacterial RNA polymerases: the whole story. Current Opinion in Structural Biology 13: 1–9.

Murakami K, Masuda S, Campbell E, Muzzin O and Darst S (2002) Structural basis of transcription initiation: an RNA polymerase holoenzyme–DNA complex. Science 295: 1285–1290.

Murakami K, Masuda S and Darst S (2002) Structural basis of transcription initiation: RNA polymerase holoenzyme at 4 Å resolution. Science 295: 1280–1284.

Murakami KS, Masuda S, Campbell EA, Muzzin O, Darst S et al. (2002) Structural basis of transcription initiation: an RNA polymerase holoenzyme‐DNA complex. Science 296: 1285–1290, pdb accession code 1L9Z.

Ptashne M and Gann A (2002) Genes and Signals. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.

Schultz SC, Shields GC and Steitz TA (1991) Crystal structure of a CAP‐DNA complex: the DNA is bent by 90 degrees. Science 253: 1001–1007, pdb accession code 1CGP.

Wagner R (2000) Transcription Regulation in Procaryotes. Oxford: Oxford University Press.

Vassylyev D, Sekine S, Laptenko O et al. (2002) Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 Å resolution. Nature 417: 712–719.

Zhang X, Chaney M, Wigneshweraraj S et al. (2002) Mechanochemical ATPases and transcriptional activation. Molecular Microbiology 45: 895–903.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Busby, Stephen JW, and Savery, Nigel J(Jan 2007) Transcription Activation at Bacterial Promoters. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000855.pub2]